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Gene Therapy in a New Light

A husband-and-wife team's experimental genetic treatment for blindness is renewing hopes for a controversial field of medicine

Born with a disease that has robbed her eyesight, Alisha Bacoccini (being examined by surgeon Albert Maguire) is undergoing experimental gene therapy at the University of Pennsylvania. If she weren't legally blind, says the 20-year-old massage therapist, she would want to be a forensic scientist.
(Stephen Voss)

Bacoccini is part of a second phase of the study that gave three LCA patients a larger dose of gene therapy than the first three volunteers received. One of the other patients in Bacoccini's group is a 9-year-old Belgian boy, who has shown some of the most dramatic improvement yet. He can see details of faces for the first time and no longer needs a special magnifying device to see the chalkboard at school. The younger the patient, Bennett and Maguire believe, the better chance the couple has of reversing blindness caused by LCA. Eventually they hope to treat babies.

Biomedical research often involves large teams of collaborators, but gene-therapy studies are an extreme case. Last year's paper in the New England Journal of Medicine announcing the initial success of gene therapy for blindness listed 32 co-authors, from the molecular biologists who designed the virus to the Italian doctors who found the patients. Bennett, the lead author, steers this group from a small office outside her laboratory. The space is crammed with notebooks and folders and decorated with thumbtacked photographs of her three kids, journal covers and a few pictures of Lancelot, now 8 years old and still seeing well.

Maguire claims that his role of giving patients injections is minor: "I just load the trucks." But he is, after all, one of the clinical experts. "With [inherited blindness] diseases, there's a huge emotional overlay," he says. "Doctors have always regarded them as incurable and told patients there is nothing we can do for you. The fact that this seems to be working is extremely exciting."

The success of the LCA trial has brought Bennett and Maguire a lot of attention—"an uncomfortable amount of attention," he says—including invitations from members of Congress to brief them on the work. But the duo seem to take it in stride. Bennett has been fielding a half-dozen phone calls and e-mails a day from blind patients or their parents who have heard about the LCA study. "I answer them all. All of these people are really, really upset about going blind or being blind," she says. To be sure, they are unlikely to fit into the LCA trial because they don't have the right genetic glitch. But she tells them to be tested for blindness genes anyway because a gene-therapy treatment for their disease may surface within a few years.

Soon Maguire and Bennett expect to begin experiments with Abyssinian cats with LCA caused by a gene mutation different from the one they've focused on so far. They're also planning a gene-therapy clinical trial for a form of Stargardt disease, or juvenile macular degeneration, which affects some 25,000 people in the United States and which they've successfully treated in mice engineered to have the disease. Now that it's been shown that gene therapy can be performed safely in the eye, companies are exploring ways to use the technique to treat diseases that aren't necessarily genetic in origin. For instance, introducing a gene that controls blood vessel growth might slow age-related macular degeneration, which afflicts more than ten million Americans.

Despite their high-flying medical successes, Bennett and Maguire drive to work in beat-up, ten-year-old cars. At home, she unwinds by gardening and playing her grandmother's grand piano, and he paints detailed, folk art-style farm scenes—rendering "every blade of grass," Bennett says. ("There's a little obsessive-compulsive disorder," Maguire explains about his hobbies.) Their youngest child has gone off to college, but they care for two dogs, an aquarium of fish and turtles and about 15 finches—Maguire's latest hobby is observing bird behavior. The family "has a high threshold for clutter," Maguire says.

Bennett stays up late at night writing reports and grant applications and planning more experiments. She is as driven as her father was when he worked on the gas laser. "There's this incredible excitement that you're about to break a barrier in something," she says.

Jocelyn Kaiser covers biomedical research and policy for Science magazine.Stephen Voss recently photographed environmental degradation in China. Both live in Washington, D.C.

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